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Category: genetics

The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

An interesting review on adenoviral cell entry and trafficking. Its discussion of how species B adenoviruses tolerate lower endosomal pH and accumulate in later-endosomal compartments before escaping were particularly intriguing. Link.

Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses.

Opposing protein pathways steer skin stem cells toward renewal or repair

Two proteins with opposing functions orchestrate the development and maintenance of healthy skin, Stanford Medicine researchers have found. Modulating their activity with topical drugs could reduce inflammation, aid wound healing and slow or halt the growth of skin cancer, the researchers believe. The findings are published in the journal Science.

The proteins are part of a family called ubiquitin-like proteins. Ubiquitination controls the targeted destruction and disposal of unneeded proteins in a cell. But in the skin, certain ubiquitin-like proteins instead switch on or off wide swaths of genes involved in cellular growth and development, the study found. In particular, they trigger progenitor (stem) cells in the lower layer of the skin to either mature and migrate to the skin surface or to self-renew.

“These two ubiquitin-like protein systems are remarkably dedicated and opposite in their functions,” said Paul Khavari, MD, Ph.D., chair of dermatology at the Stanford School of Medicine and senior author of the study. “One promotes the stem-cell state while the other drives differentiation. It’s like having two opposing forces that determine a cell’s fate.”

First 3D views of human cone opsins reveal how daylight vision reacts so fast

The retina of the human eye contains 6–7 million cone cells. These cells contain light-sensitive proteins known as cone opsins. They enable us to perceive our surroundings in detail in daylight. They allow us to see the world in thousands of colors: red strawberries, green leaves, the blue sky. They also enable us to see all the objects around us clearly. And they allow us to perceive fast movements, such as the rush of a train or the flight of a dragonfly.

Often, however, these all-rounders of daylight vision are also involved in retinal diseases. Impairment of cone receptor function, caused by genetic mutations or other degenerative processes, can lead to disorders such as color blindness and age-related macular degeneration (AMD), a disease affecting the central retina and causing progressive vision loss.

In a new study, Polina Isaikina and Sarah L. Schmidt, two researchers from the Center for Life Sciences at PSI, have succeeded for the first time in determining the three-dimensional structure of human cone opsins in their dark state and showing how their molecular architecture enables their rapid activation by light.

Teaching AI to Invent Enzymes Nature Never Imagined

Evolution is an extraordinary engine for enzymatic diversity, yet the chemistry it has explored remains a narrow slice of what DNA can encode. Deep generative models can design new proteins that bind ligands, but none have created enzymes without pre-specifying catalytic residues.

In this webinar, Chenghao Liu and Jarrid Brooks from the Arnold Lab at Caltech will introduce DISCO (DIffusion for Sequence-structure CO-design). This multimodal model co-designs protein sequence and 3D structure around arbitrary biomolecules, as well as inference-time scaling methods that optimize objectives across both modalities. Conditioned solely on reactive intermediates, DISCO designs diverse heme enzymes with novel active-site geometries. These enzymes catalyze new-to-nature carbene-transfer reactions, including alkene cyclopropanation, spirocyclopropanation, B-H, and C(sp^3)-H insertions, with high activities exceeding those of engineered enzymes. Random mutagenesis of a selected design further confirmed that enzyme activity can be improved through directed evolution. By providing a scalable route to evolvable enzymes, DISCO broadens the potential scope of genetically encodable transformations.

Is This the Key to Never Getting Old?

Awesome results and a new project to double mice lifespan. If I could fund one researcher right now it would be this man.

In this Conference talk, Dr. Greg Fahy presents stunning data from the TRIIM and TRIIM-X trials. His team has successfully regrown the human thymus in older adults, reversed epigenetic aging clocks by up to two years, and restored immune function to levels seen decades earlier.

Beyond the lab results, participants showed dramatic real-world improvements: 15% stronger muscles, 21% better VO2 max, and frailty scores dropping to near zero. Dr. Fahy also unveils the \.

Sugar-coated nanoparticles show promise for treating most aggressive form of brain cancer

Researchers at Oregon State University have potentially found a new way to treat the most aggressive form of brain cancer, glioblastoma, whose two-year survival rate is less than 30%.

The study, led by Oleh Taratula, Olena Taratula and Yoon Tae Goo of the OSU College of Pharmacy, addresses what they describe as the two most persistent obstacles to effective glioblastoma treatment: delivering therapeutic agents through the blood-brain barrier, the cell network that acts as a security checkpoint between the bloodstream and the central nervous system, and then getting those agents to preferentially target tumors.

In research published in the Journal of Controlled Release, the scientists demonstrate the novel treatment technique in a mouse model. They loaded lipid nanoparticles with genetic material that promotes tumor suppression, then coated the nanoparticles with a type of sugar. The result was a 50% median increase in glioblastoma survival time.

New effort will get genome sequences for entire Endangered Species list

The US Endangered Species Act compels the government to identify species at risk of extinction and devise plans to restore populations and the habitats they depend on. It has seen some spectacular successes, such as the restoration of the bald eagle to much of its original range. But over 2,300 plant and animal populations remain on the list, requiring ongoing government intervention.

On Thursday, it was announced that all of those species would see their genomes sequenced and tissue samples preserved to aid future conservation efforts. The work will be done by a partnership between two unexpected parties. One is the US government, which has generally attempted to undercut the Endangered Species Act as part of its anti-regulatory efforts. It is joined by Colossal Biosciences, a biotech company that has a controversial take on what actually constitutes a species.

Colossal has always said it had a conservation focus, but its headline-grabbing efforts have been directed toward restoring species that have been driven to extinction. It intends to do that by developing a combination of gene editing and reproductive technologies that it expects it can profitably license. But its dire wolf announcement, in which only a tiny handful of genetic changes were edited in to grey wolves, have raised some questions about its seriousness regarding these efforts.

X-ray snapshots reveal how viral shells change shape as they dry out

When viruses travel through the air in tiny droplets, they can quickly start to dry out. Yet many viruses remain infectious after rehydration—something that is still not fully understood. Now, an international team of researchers has directly observed at the European XFEL how the protein shells of viruses can change shape during dehydration, offering new clues to viral resilience and opening new possibilities for virology research. The results, published in Light: Science & Applications, lay the groundwork for potential applications in virology and public health and can, for instance, help develop antiviral strategies.

At the SPB/SFX instrument of the European XFEL, Abhishek Mall from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg (MPSD) and his colleagues explored the structural dynamics of the protein shells—called capsids—that enclose the genetic material of viruses. Specifically, they examined the behavior of capsids of the bacteriophage MS2 under conditions of dehydration. MS2 is an icosahedral, i.e., shaped by 20 triangular surfaces that form a sphere, single-stranded RNA virus that infects the bacterium Escherichia coli and is widely used as a model system in virology.

The capsid’s design is critical for protecting the viral genome and helping the virus interact with host cells. However, viruses are often confronted with environments that challenge their structural integrity, for example through dehydration. Theoretical studies have long suggested that capsids may undergo low-energy “buckling transitions”—sudden changes in shape—to adapt to such stresses, but direct experimental evidence has been lacking.

Out of darkness, blind Mexican cavefish illuminate brain evolution

Deep within the dark caves of northeastern Mexico lives a fish that has spent hundreds of thousands of years adapting to a world without light. The blind Mexican cavefish (Astyanax mexicanus) has evolved in perpetual darkness, losing its eyes and pigmentation while developing remarkable adaptations that help it survive in nutrient-poor environments.

Now, scientists are using this extraordinary species to uncover how evolution rewires the brain and shapes behavior. Because Astyanax exists both as sighted surface fish and as more than 30 independently evolved cave populations, researchers can directly compare how life in darkness alters sensory systems, neural circuits and behavior.

With new genetic tools and advanced imaging technologies that allow scientists to watch brain activity in real time, this unique fish is providing unprecedented insights into how animals adapt to extreme environments—and how evolution transforms the brain itself.

Synthetic DNA toolkit expands scientists’ ability to recognize genetic targets

A new method for recognizing and targeting DNA that dramatically expands the range of genetic sequences scientists can identify has been developed by experts at the University of Portsmouth. Published this week in Nature Communications, the research opens new possibilities for gene-targeting technologies, molecular diagnostics and DNA nanotechnology.

Dr. David Rusling, associate professor in bioengineering from the University of Portsmouth’s School of Medicine, Pharmacy and Biomedical Sciences, said, Our lab develops synthetic molecules that can recognize and bind to unique gene sequences. By introducing synthetic DNA bases into these molecules, we’ve been able to significantly improve how they recognize their targets.

I’ve worked in this area for around 20 years, and this is the first time we’ve had a system that combines strong recognition under physiological conditions with building blocks that are commercially available to other researchers.

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